Spine, 2004 Jul 1, 29(13), 1447 - 51 Spondylocostal dysostosis: thirteen new cases treated by conservative and surgical means; Teli M et al.; STUDY DESIGN: Prospective assessment of a cohort of patients affected by spondylocostal dysostosis . OBJECTIVE: To report on the results of conservative and operative management of spondylocostal dysostosis and, based on this, to propose an assessment and treatment protocol for the condition . SUMMARY OF BACKGROUND DATA: Spondylocostal dysostosis and spondylothoracic dysostosis are subtypes of Jarcho-Levin syndrome, a hereditary condition manifested by vertebral body and related rib malformations . Mortality prevails in spondylothoracic dysostosis because of more severe respiratory compromise . METHODS: Details of prenatal and postnatal diagnosis, history, and management of 13 patients with spondylocostal dysostosis are presented . All patients were treated postnatally with repeated chest physiotherapy . Two patients refractory to conservative treatment underwent surgical intervention: the first had a chest wall reconstruction via a latissimus dorsi flap, the second a posterior spinal instrumented fusion for progressive scoliosis . RESULTS: Prenatal ultrasound in 4 of 13 cases showed full details of vertebral and rib anomalies . Thoracic and lumbar hemivertebrae were most common, leading to congenital scoliosis in 10 of 13 cases . A number of extraskeletal abnormalities were also identified . At an average follow-up of 4.5 years, the survival rate was 100% with a remarkable decrease of the rate of respiratory complications . Surgical treatment in selected cases led to satisfactory results . CONCLUSIONS: Prenatal diagnosis of spondylocostal dysostosis allows exclusion of spondylothoracic dysostosis and aids genetic counseling in quantifying the risk to siblings . Postnatally, prompt management of these patients with physiotherapy leads to prolonged survival . Surgical intervention may then be indicated to stabilize chest wall or spine deformities, with promising results. Respir Care, 2004 Jul, 49(7), 783 - 92 Evidence-based asthma management; Kallstrom TJ; In 2002 the National Asthma Education and Prevention Program published evidence-based guidelines for the diagnosis and management of asthma, but there are some unresolved asthma-management issues that need further research . For asthmatic children inhaled corticosteroids are more beneficial than as-needed use of beta(2) agonists, long-acting beta(2) agonists, theophylline, cromolyn sodium, nedocromil, or any combination of those . Leukotriene modifiers are an alternative but not a preferred treatment; they should be considered if the medication needs to be administered orally rather than via inhalation . Cromolyn sodium and nedocromil are effective long-term asthma-control medications, but they are not as effective as inhaled corticosteroids . There is insufficient evidence to determine whether cromolyn benefits maintenance of childhood asthma . Cromolyn sodium and nedocromil are alternatives, but not preferred treatments for mild persistent asthma . Cromolyn may be useful as a preventive therapy prior to exertion or unavoidable exposure to allergens . Regular inhalation of corticosteroids controls asthma significantly better than as-needed beta(2) agonists . No studies have examined the long-term impact of regular inhaled corticosteroids on lung function in children <or= 5 years old . As monotherapy, inhaled corticosteroids are more effective than long-acting beta(2) agonists . The asthma-control benefit of inhaled corticosteroids decidedly outweighs the risks from inhaled corticosteroids . There is no high-level evidence that low-to-medium-dose inhaled corticosteroids have ocular toxicity or important effects on hypothalamic-pituitary-adrenal function in children . Antibiotic therapy has no role in asthma management unless there is a bacterial comorbidity, but further research is needed on the relationship between sinusitis and asthma exacerbation . The asthma care plan should include a written asthma action plan for the patient, but there is inadequate evidence as to whether the asthma action plan should be based on symptoms or on peak flow monitoring . There is low-level evidence that helium-oxygen mixture (heliox) may be of benefit in the first hour of an acute asthma attack but less advantageous after that first hour . Metered-dose inhalers are no more or less effective, overall, than other aerosol-delivery devices for the delivery of beta(2) agonists or inhaled corticosteroids, so the least expensive delivery method should be chosen. Int J Clin Pharmacol Ther, 2004 Jun, 42(6), 307 - 13 Influence of rifampin on serum markers of cholesterol and bile acid synthesis in men; Lutjohann D et al.; OBJECTIVE: It has been demonstrated in preliminary studies that rifampin, a semisynthetic antibiotic and known inducer of hepatic cytochrome P450 3A4, reduces serum concentrations of total bile acids only in individuals with liver disease and elevated serum bile acid levels . METHODS: We studied the effect of rifampin on concentrations of surrogate serum markers of cholesterol and bile acid synthesis as well as of cholesterol absorption in 10 male subjects before and after administration of rifampin (600 mg/day) for 6 days . Cholesterol and its precursors were analyzed by gas-liquid chromatography (GLC), bile acid intermediates and individual bile acids by isotope-dilution methods using GLC-mass spectrometry (MS) or by high-performance liquid chromatography (HPLC) . RESULTS: Treatment with rifampin resulted in a 70% increase (p = 0.008) of the serum concentration of the bile acid precursor 7alpha-hydroxy-4-cholesten-3-one, which is a marker for bile acid production . Serum total cholesterol was not altered, however, treatment with rifampin elevated the ratio of lathosterol to cholesterol, an indicator of cholesterol synthesis, by 23% (p = 0.037) . Interestingly, serum concentration of total bile acids decreased slightly by 29% (p = 0.022), mainly due to a lowering of the secondary bile acid, deoxycholic acid (-60%; p = 0.005) . CONCLUSION: A 6-day treatment with rifampin induces a reduction of deoxycholic serum concentrations in healthy men associated with a moderate increase of serum markers of bile acid and endogenous cholesterol synthesis. J Heart Valve Dis, 2004 May, 13(3), 494 - 9; discussion 499-500 Could 37 degrees C storage temperature extend homovital valve allograft viability? Baric D, Cebotari S, Mertsching H, Leyh R, Haverich A. BACKGROUND AND AIM OF THE STUDY: Preservation of allograft valves is the most important determinant of their durability . Unprocessed, homovital valve allografts stored at 4 degrees C in nutrient medium have provided superior mid-term results over routinely used cryopreserved or antibiotic-sterilized allografts . As storage temperature may alter viability, it was hypothesized that allograft storage at 37 degrees C may maintain greater viability over time . METHODS: Porcine aortic (n = 10) and pulmonary valve conduits (n = 10) were harvested under sterile conditions . Valve leaflets and sinus walls were separated, and each was divided into two specimens, which were stored in modified culture medium at 4 degrees C and 37 degrees C, respectively . Cell viability was tested by monitoring metabolic activity at 37 degrees C at days 1, 3, 7, 10, and 14 . The proliferative ability of cells isolated from valve leaflets was assessed after 14 days by cell culture . Sterility testing of the storage medium was also carried out . RESULTS: Valve leaflet cells and sinus wall cells had significantly higher metabolic activity when stored at 37 degrees C . The median number of isolated cells at 4 degrees C was 3,231.5 (range: 422-3,844), and at 37 degrees C was 8,317.50 (range: 4,329-8,650) . The storage medium was sterile in all cases . CONCLUSION: Storage at 37 degrees C significantly improved valve allograft cell metabolic activity and viability compared with storage at 4 degrees C for up to 14 days . The lower concentration of antibiotics did not affect the sterility of tissues stored at 37 degrees C. Amino Acids, 2004 Jun, 26(3), 283 - 9 Epub 2003 Oct 17. Synthesis and investigation of a new cyclo (Nalpha-dipicolinoyl) pentapeptide of a breast and CNS cytotoxic activity and an ionophoric specificity; Abo-Ghalia M et al.; A new acylated cyclopentapeptide namely, Cyclo-( N(alpha)-dipicolinoyl)- bis-{ L-Leu-DL-Nval}- L-Lys OMe (5) was suggested and synthesized . The structural conception of 5 was rationalized by analogy to the structural features of some known cyclodepsipeptides exemplified by the antibiotic and DNA intercalator actinomycin D (NSC: 3053), the ionophore and anti-HIV enniatin B (NSC: 692895) and the ionophore and antibiotic valinomycin (NSC: 630175) . The cyclopeptide 5 was chemically synthesized, starting from its linear tetrapeptide ester precursor 2 by coupling L-lysine methyl ester to the prepared tetrapeptide acid 3 or hydrazide 4 via the mixed anhydride or azide method, respectively . A cytotoxic activity (cell killing) in both breast (NCF7) and CNS (SF-268) cell lines NCI, USA) was realized for 5, while less active cytotoxic profile was determined for 2 . Moreover, we have recently reported general ionophoric and sensor characteristics particularly, for Pb (II) ions for both 5 and 2 . Correlation between the cytotoxic activity and the ionophoric potency is a matter of future investigations. Ann Hematol, 2004 Sep, 83(9), 573 - 7 Epub 2004 Jun 19. Ganciclovir-related neutropenia after preemptive therapy for cytomegalovirus infection: comparison between cord blood and bone marrow transplantation; Tomonari A et al.; We studied ganciclovir (GCV)-related neutropenia after preemptive therapy for cytomegalovirus infection: 9 of 17 (53%) cord blood transplantation (CBT) patients and 18 of 20 (90%) bone marrow transplantation (BMT) patients developed GCV-related neutropenia with an absolute neutrophil count (ANC) of less than 1,000/microl . Among the patients who did not receive granulocyte colony-stimulating factor, 2 (13%) and 1 (7%) CBT patients, and 10 (56%) and 8 (44%) BMT patients, developed neutropenia with an ANC of less than 500 and 250/microl, respectively . The incidences of neutropenia in patients with an ANC of less than 1,000, 500, and 250/microl were significantly lower after CBT in comparison with BMT . Two BMT patients, but no CBT patients, developed neutropenic fever, and both patients recovered after antibiotic therapy . In CBT patients, a creatinine clearance rate of less than 50 ml/min and an absence of steroid therapy were associated with a greater incidence of GCV-related neutropenia . No risk factors for GCV-related neutropenia were found in BMT patients . These results suggest that GCV may be less toxic to myeloid progenitor cells from cord blood than those from bone marrow. J Endod, 2004 Jul, 30(7), 541 - 7 Management of extra oral sinus cases: a clinical dilemma; Mittal N et al.; The cutaneous sinus tract of dental origin is an uncommon but well documented condition . Its diagnosis is not always easy unless the treating clinician considers the possibility of its dental origin . Such patients may undergo multiple surgical excisions, biopsies, and antibiotic regimens, but all of them fail with the recurrence of the sinus tract . This is because the primary etiology is incorrectly diagnosed . This case report describes the treatment of four patients presenting with variable complaints of pain and purulent or hemorrhagic discharge from lesions of the face . Clinical and radiographic examination revealed carious teeth with radiolucent areas indicating chronic periradicular abscess . The teeth were restorable, so nonsurgical endodontic therapy was performed in all of them . No systemic antibiotic therapy was provided . The patients responded well, and the cutaneous lesions healed uneventfully . Improper diagnosis can lead to needless loss of teeth that can be otherwise maintained through timely and proper management. Prev Vet Med, 2004 Jun 10, 64(1), 27 - 40 Within-herd spread of contagious bovine pleuropneumonia in Ethiopian highlands; Lesnoff M et al.; Contagious bovine pleuropneumonia (CBPP) is a major threat for cattle health and production in Africa . This disease is caused by the small-colony type of Mycoplasma mycoides subspecies mycoides (MmmSC) . Transmission occurs from direct and repeated contacts between sick and healthy animals . Veterinary services recently reported a resurgence of CBPP in the province of West Wellega, in the Ethiopian highlands . A research program was set up to estimate the epidemiological parameters of the within-herd infection spread . A follow-up survey was implemented in 71 sampled herds of the Boji district (West Wellega province) . Fifteen herds were classified as newly infected and used in a serological- and clinical-incidence study . The overall 16-month cumulative sero-incidence risk was 34% . Clinical cases were recorded for 39% of the seropositive cattle; case-fatality risk was 13% . There was no evidence of benefit on infection spread of CBPP-control measures used locally by farmers (isolation or antibiotic treatments of sick animals) . This might be related to a lack of power in the statistical analyses or to a quality problem for the medications used (and more generally, for health-care delivery in the Boji district). Nefrologia, 2004, 24 Suppl 3, 16 - 20 {Fever and cavitary infiltrate in a renal transplant recipient}; Rocamora N et al.; Aspergillus infection is a rare but devastating complication following organ transplantation with high mortality rate . Aspergillus fumigatus is the most common cause of invasive aspergillosis . This fungus is present in the environment worldwide . Aspergillus infection is mainly acquired by inhalation of spores and several nosocomial infections in transplant recipient have been associated with construction work at hospitals . Risk factors for invasive aspergillosis include administration of steroid boluses, history of cytomegalovirus infection, neutropenia and prolonged antibiotic use after transplantation . Successful treatment depends on three factors: early diagnosis, aggressive antifungal therapy and decrease or removal of immunosuppression . Amphotericin deoxycholate has been the standard treatment for many years but lipid preparations for amphotericin are now used due to their significantly fewer adverse effects . A number of new antifungal drugs are now being developed including new azoles such as voriconazol and echinocandin . Invasive aspergillosis has a high mortality rate more than 95% when cerebral dissemination is demonstrated . We report the case of a 47 years old woman who received a cadaveric renal graft and developed pulmonary aspergillosis with fulminant cerebral dissemination two months later . The diagnosis of pulmonary aspergillosis was by culture isolation obtained from bronchioalveolar lavage . Removal of immunosuppresive agents and liposomal amphotericin B therapy were started shortly after admission . Brain CT scan performed on the 12th day showed cerebral dissemination . The recipient died two days later . Our patient had several risk factors such as the administration of steroid boluses and cytomegalovirus infection . Invasive aspergillosis must be always included in the differential diagnosis of fever and pulmonary disease in the renal transplant recipient. Proc Natl Acad Sci U S A, 2004 Jul 6, 101(27), 10036 - 41 Epub 2004 Jun 24. Mass spectrometric characterization of a three-enzyme tandem reaction for assembly and modification of the novobiocin skeleton; Pi N et al.; The tripartite scaffold of the natural product antibiotic novobiocin is assembled by the tandem action of novobiocin ligase (NovL) and novobiocic acid noviosyl transferase (NovM) . The noviosyl ring of the tripartite scaffold is further decorated by a methyltransferase (NovP) and a carbamoyltransferase (NovN), resulting in the formation of novobiocin . To facilitate kinetic evaluation of alternate substrate usage by NovL and NovM toward the creation of variant antibiotic scaffolds, an electrospray ionization/MS assay for obtaining kinetic measurements is presented for NovL and NovM separately, in each case with natural substrate and the 3-methyl-4-hydroxybenzoic acid analog . Additionally, assays of tandem two-enzyme (NovL/NovM) and three-enzyme (NovL/NovM/NovP) incubations were developed . The development of these assays allows for the direct detection of each intermediate followed by its utilization as substrate for the next enzyme, as well as the subsequent formation of final product as a function of time . This MS tandem assay is useful for optimization of conditions for chemoenzymatic generation of novobiocin and is also suitable for evaluation of competitive usage of variant substrate analogs by multiple enzymes . The studies presented here serve as a platform for the subsequent expansion of the repertoire of coumarin-based antibiotics. J Anim Sci, 2004 Jun, 82(6), 1764 - 72 Spray-dried plasma improves growth performance and reduces inflammatory status of weaned pigs challenged with enterotoxigenic Escherichia coli K88; Bosi P et al.; We investigated whether spray-dried plasma (SDP) improved growth and health of piglets challenged with enterotoxigenic Escherichia coli K88 (ETEC) . Forty-eight pigs weaned at 21 d (BW = 4.88 +/- 0.43 kg) received one of four diets containing 6% SDP or fish proteins (as-fed basis) either nonmedicated (SDP-NM and FP-NM diets) or medicated with 0 or 250 mg/kg of colistine + 500 mg/kg of amoxycycline (SDP-M and FP-M diets), for 15 d . On d 4, pigs were orally challenged with ETEC . On d 15, eight pigs per dietary group were killed, blood and saliva were collected for analysis of K88 fimbriae-specific immunoglobulin (Ig)-A, and jejunum was removed for villi preparation, histological analysis, and cytokine expression . The presence or absence of K88 receptors (K88+ and K88- pigs respectively) was determined by villous adhesion assay . Effects of protein source on ADG (P = 0.04) and ADFI (P < 0.01), as well of medication on ADFI (P < 0.02), of all pigs were observed . In sacrified pigs, there was an effect of protein source on ADG (P = 0.03) and ADFI (P < 0.001), as well an interaction between medication and presence of K88 receptor (P = 0.02) for feed:gain ratio . Plasma K88 specific IgA were low in all K88 pigs and higher in K88+ pigs fed FP-NM compared with all the other groups (P < 0.05), except SDP-M . An interaction was found among protein source, medication, and presence of K88 receptors (P = 0.04) . Saliva IgA concentrations were high in all pigs fed FP-NM and low in all other pigs . Jejunum of pigs fed FP-NM showed some ulcerations, edema, and mild inflammatory cell infiltration (ICI) . In pigs fed FP-M, edema was reduced . Conversely, only a mild ICI was observed in pigs fed SDP-NM and SDP-M . Crypt depth was increased in K88+ pigs fed SDP-NM and an interaction between protein source and presence of K88 receptors was observed (P < 0.05) . Expressions of tumor necrosis factor-alpha and interleukin (IL)-8 were lower in pigs fed SDP-NM and SDP-M than in those fed FP-NM and FP-M, either K88- or K88+ (P < 0.01) . In pigs fed FP diets, expression of IL-8 tended to increase (P = 0.08) in K88+ compared with K88- subjects . Expression of interferon-gamma increased in K88 and K88+ pigs fed FP-M as compared with other pigs (P < 0.01) . These results indicate that feeding with SDP improved growth performance and protected against E . coli-induced inflammatory status, and suggest that use of SDP-NM can be considered a valid antibiotic alternative. Tsitologiia, 2003, 45(8), 804 - 11 {Amphotericin B channel conductance inactivation}; Ibragimova VKh et al.; Effects induced in bilayer lipid membranes by amphotericin B and its alkyl derivatives was analysed . Inactivation of the antibiotic-dependent multichannel membrane conductance was discovered . Kinetics of membrane conductivity was shown to depend on the antibiotic concentration in the membrane . At concentrations between 10(-8) and 10(-7) M, the resulting conductance appeared to the transient . We suggest that the phenomenon of biphasic kinetics of membrane conductance is the result of a consecutive transformation of polyene channels in the membrane: half-pores are assembled on either side of membrane-nonconducting 1; two half-pores combine to build up a conducting channels-conducting 2, and the conducting channels are disassemled to monomers and nonconducting self-associated forms inside the membrane-disassembled state (nonconducting 3) . To explain the transient characteristics of the induced conductance, it is proposed that the antibiotic, present in the solution under self-associated form, binds the membrane and forms pores, then dissociates in the bilayer in a non-active monomeric form . The existence of definite monomers and nonconducting self-associated forms of amphotericin B molecules inside the membrane was estimated from the dependence of kinetic conductance of lipid membranes of amphotericin B and its alkyl derivatives, when the antibiotics are washed out from aqueous medium . Equilibrium between different antibiotic assemblies inside the membrane was demonstrated by the kinetics of conductance decrease following washing the antibiotic . Using circular dichroism measurements, we observed that amphotericin B alkyl derivatives were in self-associated form being susceptible to form pores across cholesterol-containing membranes . The phenomenon of biophasic kinetics was observed only in the cholesterol-containing membrane . The substitution of membrane cholesterol for ergosterol provides monotonic kinetics of membrane conductance at any antibiotic concentration. Biosci Biotechnol Biochem, 2004 Jun, 68(6), 1345 - 52 Identification and cloning of the gene involved in the final step of chlortetracycline biosynthesis in Streptomyces aureofaciens; Nakano T et al.; For chlortetracycline biosynthesis in Streptomyces aureofaciens, the final reduction step is essential to give an antibiotic activity to its intermediate, which is catalyzed by tetracycline dehydrogenase with 7,8-dedimethyl-8-hydroxy-5-deazariboflavin (FO) as a cofactor . We identified and cloned the gene, which is essential for the biosynthesis of 6-demethyltetracycline and participates in the final step of its biosynthesis, from the genomic DNA of the 6-demethyltetracycline producer S . aureofaciens HP77 . DNA sequence analysis revealed that the gene (tchA) had an open reading frame of 455 amino acids with an estimated molecular mass of 48.1 kDa . Southern hybridization analysis revealed that the tchA gene was located external to the chlortetracycline biosynthetic gene cluster in the genome . A conserved domain search of protein sequence databases indicated that TchA showed a similarity to FbiB, which is involved in the modification of FO in Mycobacterium bovis. Antimicrob Agents Chemother, 2004 Jul, 48(7), 2538 - 43 Effects of fluoroquinolones on the migration of human phagocytes through Chlamydia pneumoniae-infected and tumor necrosis factor alpha-stimulated endothelial cells; Uriarte SM et al.; The anti-inflammatory activities of three quinolones, levofloxacin, moxifloxacin, and gatifloxacin, were investigated with an in vitro model of transendothelial migration (TEM) . Human umbilical vein endothelial cells (HUVEC) were seeded in Transwell inserts, treated with serial dilutions of antibiotics, infected with Chlamydia pneumoniae, or stimulated with tumor necrosis factor alpha (TNF-alpha) . Neutrophils or monocytes were also preincubated with serial dilutions of each antibiotic . TEM was assessed by light microscopic examination of the underside of the polycarbonate membrane, and levels of interleukin-8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) were measured by enzyme-linked immunosorbent assay . In HUVEC infected with C . pneumoniae or stimulated with TNF-alpha, all fluoroquinolones significantly decreased neutrophil and monocyte TEM, compared to antibiotic-free controls . Moxifloxacin and gatifloxacin produced a significant decrease in IL-8 in C . pneumoniae-infected and TNF-alpha-stimulated HUVEC; however, moxifloxacin was the only fluoroquinolone that produced a significant decrease in MCP-1 levels under both conditions . Results from this study indicate similarities in the anti-inflammatory activities of these fluoroquinolones, although no statistically significant decrease in chemokine secretion was observed when levofloxacin was used . Mechanisms of neutrophil and monocyte TEM inhibition by fluoroquinolone antibiotics are unknown but may be partially due to inhibition of IL-8 and MCP-1 production, respectively. Antimicrob Agents Chemother, 2004 Jul, 48(7), 2471 - 6 Impact of fluconazole prophylaxis on cortisol levels in critically ill surgical patients; Magill SS et al.; Fluconazole is widely used in the intensive care unit for prevention and treatment of fungal infections . Case reports have described an association between fluconazole and adrenal dysfunction, an important cause of morbidity and mortality in critically ill patients . We sought to determine whether 400 mg of fluconazole per day administered to critically ill surgical patients was associated with a reduction in cortisol levels . Cortisol levels were measured in stored plasma specimens drawn from 154 critically ill surgical patients randomized in 1998-1999 to receive fluconazole or placebo for the prevention of candidiasis . The primary outcome measure was the median plasma cortisol level > or =1 day after study drug initiation (MPCL) . Secondary outcomes were adrenal dysfunction, defined as an MPCL of <15 microg/dl, changes in cortisol levels over time, and mortality . The median MPCL was 15.75 microg/dl (interquartile range {IQR}, 11.65 to 21.33 microg/dl) in 79 patients randomized to fluconazole and 16.71 microg/dl (IQR, 11.67 to 23.00 microg/dl) in 75 patients randomized to placebo (P = 0.52) . Patients randomized to fluconazole did not have significantly increased odds of adrenal dysfunction compared to patients randomized to placebo (odds ratio, 0.98; 95% confidence interval, 0.48 to 2.01) . Randomization to fluconazole was not associated with a significant difference in cortisol level changes over time . Mortality was not different between patients with and without adrenal dysfunction, nor was it different between patients with adrenal dysfunction who were randomized to fluconazole and those randomized to placebo . Fluconazole prophylaxis in this population of critically ill surgical patients did not result in significant adrenal dysfunction. Eur Rev Med Pharmacol Sci, 2003 Sep-Oct, 7(5), 127 - 30 A new approach for the treatment of bacterial vaginosis: use of polyhexamethylene biguanide . A prospective, randomized study; Gerli S et al.; BACKGROUND: Bacterial vaginosis (BV) is the most common vulvovaginal infection and represents the 35% of all the infections occurring in women in the reproductive age . It is well recognised that serious forms of BV can induce several complications among women undergoing gynaecologic or obstetric surgery, having pelvic inflammatory diseases, temporary or absolute infertility, miscarriage and abortion . At present, the clinical treatment of choice of BV is the use of systemic or local (gel or cream) metronidazole and clindamycin, though systemic use has some limitations due to side-effects and contraindications . Polyhexamethylene biguanide (PHMB) is a new bi-biguanide compound having a broad spectrum activity and low toxicity, that have been successfully utilized in ophthalmology and dentistry . Aim of this study was to evaluate the efficacy and tolerability of a single-dose vaginal administration of a PHMB vaginal gel in the treatment of BV in comparison to clindamycin vaginal cream . METHODS: One-hundred and ten patients affected by BV were treated with PHMB vaginal gel in single administration or clindamycin vaginal cream 1 daily administration for 7 days . RESULTS: We demonstrated the therapeutic efficacy of mono-dose administration of a vaginal solution containing PHMB in BV treatment; this efficacy is similar to the one shown in antibiotic therapy . Furthermore, this product was well tolerated by all treated patients . CONCLUSIONS: Mono-dose PHMB treatment should be regarded as the therapy of choice for BV, using clindamycin and metronidazole only for relapses treatment. Ann Surg, 2004 Jul, 240(1), 28 - 37 The diminishing role of surgery in the treatment of gastric lymphoma; Yoon SS et al.; OBJECTIVE: This article reviews the pathogenesis, diagnosis, and treatment of patients with primary gastric lymphoma, with special attention to the changing role of surgery . SUMMARY BACKGROUND DATA: Primary gastric lymphomas are non-Hodgkin lymphomas that originate in the stomach and are divided into low-grade (or indolent) and high-grade (or aggressive) types . Low-grade lesions nearly always arise from mucosa-associated lymphoid tissue (MALT) secondary to chronic Helicobacter pylori (H . pylori) infection and disseminate slowly . High-grade lesions may arise from a low grade-MALT component or arise de novo and can spread to lymph nodes, adjacent organs and tissues, or distant sites . METHODS: A review of the relevant English-language articles was performed on the basis of a MEDLINE search from January 1984 to August 2003 . RESULTS: About 40% of gastric lymphomas are low-grade, and nearly all these low-grade lesions are classified as MALT lymphomas . For low-grade MALT lymphomas confined to the gastric wall and without certain negative prognostic factors, H . pylori eradication is highly successful in causing lymphoma regression . More advanced low-grade lymphomas or those that do not regress with antibiotic therapy can be treated with combinations of H . pylori eradication, radiation therapy, and chemotherapy . Nearly 60% of gastric lymphomas are high-grade lesions with or without a low-grade MALT component . These lymphomas can be treated with chemotherapy and radiation therapy according to the extent of disease . Surgery for gastric lymphoma is now often reserved for patients with localized, residual disease after nonsurgical therapy or for rare patients with complications . CONCLUSION: The treatment of gastric lymphoma continues to evolve, and surgical resection is now uncommonly a part of the initial management strategy. Med Wieku Rozwoj, 2003 Oct-Dec, 7(4 Pt 2), 547 - 55 {Pharmacokinetics of netilmicin in neonates}; Piekarczyk A et al.; Our goal was to perform a pharmacokinetic analysis of netilmicin to develop the optimum dosage regimen of this antibiotic in premature neonates hospitalized in Neonate Intensive Care Unit of the Institute of Mother and Child in Warsaw . MATERIALS AND METHODS: The pharmacokinetics of netilmicin was studied in 80 neonates, divided for analysis into three groups according to gestational age: group I - 10 full-term neonates (b.w . 3225 +/-502 g); group II - 35 premature neonates between 29-32 weeks (b.w . 1134+/-311 g); and group III - 35 premature neonates between 23-28 weeks (b.w . 910 +/-243 g) . The whole studied group of neonates was initially given i.v . netilmicin every 24 h, then the dosing interval for the safety reasons was prolonged to 48 h in the premature group . The neonates received netilmicin in the following doses: group I - mean dose 6.2 +/-0.42 mg/kg; group II - 5.911+/-0.529 mg/kg and group III - 6.014+/-0.313 mg/kg . Serum netilmicin concentrations were determined by fluorescence polarization immunoassay (FPIA) - TD(x)FL(x) (Abbott) . RESULTS: The mean of pharmacokinetic parameters for groups I, II, and III were defined respectively: t(0.5) (h): 7.14+/-1.88, 12.68+/-4.26, 15.98+/-5.9; AUC0-( (microg x h/ml): 149+/-41, 303+/-100, 401+/-172; Cl/kg (l/h/kg): 0.748+/-0.24, 0.371+/-0.13, 0.289+/-0.1; MRT0-( (h): 6.3+/-2.8, 10.8+/-6.3, 15.5+/-9.3; V(dss) (l/kg): 0.75+/-0.24, 0.59+/-0.52, 0.44+/-0.19 . The obtained mean netilmicin serum concentrations (microg/ml) were: once-a-day dosage: C(max) - 10.25+/-2.616 (group I), 12.2+/-2.65 (group II), 12.9+/-2.77 (group III); C(min) - 1.158+/-0.657 (group I), - 2.65+/-1.02 (group II), 3.23+/-1.42 (group III); once-a-48 h dosage: C(max) - 11.7+/-1.09 (group II), 13.9+/-6.53 (group III); C(min) - 1.09+/-0.64 (group II), 1.74+/-0.98 (group III) . CONCLUSIONS: 1 . All the calculated pharmacokinetic parameters in the premature neonate groups (group II and III) significantly differs from the parameters calculated for full-term neonates . 2 . Significant correlations were obtained between birth weight, gestational age and all the calculated pharmacokinetic parameters in all the groups of neonates . 3 . The obtained results indicated that the use of the dosing schedule of netilmicin with the dose intervals of 48 h in premature neonates should guarantee adequate peak and trough levels without the need of routine monitoring of each patient in the premature neonate group except the very low weight neonates . Detection of the specific sensitivity of lymphocytes T during the diagnosis of food allergy. Dis Aquat Organ, 2004 Apr 21, 59(1), 75 - 8 Appendage deformity syndrome--a nutritional disease of Macrobrachium rosenbergii; Kumar AR et al.; Culture of the freshwater prawn Macrobrachium rosenbergii as an alternative to penaeid shrimp has recently increased in coastal areas of southern India in order to avoid numerous problems, particularly with white spot syndrome virus (WSSV) . However, M . rosenbergii culture is now threatened by a new disease, appendage deformity syndrome (ADS), that also results in high mortality . Analysis of ADS prawns for viruses such as WSSV, monodon baculovirus (MBV) and infectious hypodermal and hematopoeitic necrosis virus (IHHNV) gave negative results . ADS prawns were also negative for bacterial pathogens and affected animals did not respond to antibiotic therapy . A study of potential nutritional deficiency revealed that carotenoid supplementation in the diet led to a significant decrease in ADS prawns. Pediatr Pulmonol, 2004 Aug, 38(2), 129 - 34 Cyproheptadine is an effective appetite stimulant in cystic fibrosis; Homnick DN et al.; Chronic pulmonary infection and intestinal malabsorption often lead to malnutrition in children and adults with cystic fibrosis (CF) . Appetite stimulants, along with provision of adequate calories, may aid in overcoming nutritional deficits, allowing a better prognosis . We undertook a trial of cyproheptadine hydrochloride (CH) to determine its effectiveness as an appetite stimulant in 18 adults and children with CF . This was a 12-week, randomized, double-blind, controlled trial of CH vs . placebo . Eighteen subjects with documented CF (sweat or genetics positive), minimum age of 5 years, and ideal body weight for height <100% were entered, and 16 completed the study . Subjects were seen at baseline and every 4 weeks . Measures included baseline demographics, Shwachman score, anthropometrics (weight, height, body mass index, skin folds, and body composition by bioelectric impedance analysis), spirometry, caloric intake, days of oral (PO) and intravenous (IV) antibiotics, and a symptom and satisfaction survey . Subjects in the CH group showed significant increases in weight (mean 3.45 kg vs . 1.1 kg in the placebo group), height, BMI percentiles, ideal body weight/height, weight for age z-scores, and fat and fat-free mass . There were no changes or differences in PO or IV antibiotic use or spirometric changes . No significant side effects except transient mild sedation occurred in the CH group . Patient acceptance was good . In conclusion, CH appears to be an effective appetite stimulant with minimal side effects in children and adults with CF . Patient Educ Couns, 2004 Jul, 54(1), 21 - 5 Acne vulgaris: myths and misconceptions among patients and family physicians; Brajac I et al.; The objective of the study was to evaluate the health beliefs and knowledge about acne among acne patients and family physicians . A total of 100 patients referred to a dermatologist for management of acne vulgaris and 120 family physicians completed questionnaires . The questionnaires consisted of questions about health beliefs, the natural course of the disease, the causes of acne, and a set of questions about the knowledge of acne therapy . Acne was considered as a trivial and transitory condition by 52% of the acne patients and 44% of the family physicians . The overall score of correct answers pertaining to the causes of acne among the acne patients and family physicians was 11 and 15%, respectively . The percentage of correct answers regarding the natural course of the disease was 6% for both subsets of subjects . Acne was believed to be curable by 96% of acne patients . Most patients (66%) believed that acne would improve immediately after the first treatment . The knowledge of isotretinoin teratogenecity was reasonable among family physicians (55% correct answers), but it was much lower for other side effects (9%) . The overall score of correct answers regarding antibiotic therapy among family physicians was only 21% . Impact of the disease was underestimated by family physicians and also by acne patients . Overall knowledge pertaining to the causes, natural course and therapy was very low . Myths and misconceptions still exist among patients but also among family physicians. Diabet Med, 2004 Jul, 21(7), 705 - 9 Swab cultures accurately identify bacterial pathogens in diabetic foot wounds not involving bone; Slater RA et al.; AIMS: Current clinical practice assumes swab cultures from wounds are unreliable . However, this assumption is based upon data culled only from wounds in which osteomyelitis and/or gangrene were present . This study aimed to re-evaluate the accuracy of swab cultures vs . deep tissue cultures in diabetic wounds of varying depth and severity . METHODS: A total of 60 infected diabetic foot wounds were cultured . Two specimens were taken from each wound: superficial swab before debridement and deep tissue specimen towards the end of surgical debridement . RESULTS: In 37 wounds (62%), the micro-organisms isolated from the swab specimen and those isolated from the deep tissue specimen were identical . In another 12 wounds (20%), the swab culture contained all micro-organisms isolated from the deep tissue culture, but also contained additional micro-organisms . Analysis according to the depth of the wound, demonstrated that swabs identified all micro-organisms isolated from the deep tissue specimens in 36/40 wounds (90%) that did not extend to bone as opposed to 13/20 wounds (65%) that extended to bone . CONCLUSIONS: Swab cultures are valuable in identifying pathogens in diabetic foot wounds when bone is not involved . When surgical debridement is contraindicated or delayed, swab cultures can be used to select appropriate antibiotic therapy. Bone Marrow Transplant, 2004 Jul, 34(1), 51 - 6 A randomized trial of amifostine as a cytoprotectant for patients receiving myeloablative therapy for allogeneic hematopoietic stem cell transplantation; Hwang WY et al.; We initiated a randomized study of amifostine (the organic thiophosphate formerly known as WR-2721) given to patients during myeloablative conditioning therapy for allogeneic bone marrow transplantation . Amifostine was given at a dose of 1000 mg/day of conditioning and was well tolerated if attention was given to serum calcium levels, blood pressure and antiemetics . Since August 1998, 60 patients (30 on each arm) have completed the study . There was no significant difference in the days to neutrophil or platelet engraftment in either arm of the study . Significantly, the duration of grade I-IV mucositis was decreased in the group that received amifostine (P=0.02) . Also grade III or IV infections (P=0.008), duration of antibiotic therapy (P=0.03) and duration of fever (P=0.04) were significantly reduced with amifostine . However, there were no differences in the incidence of grade III or IV mucositis, liver toxicity or renal toxicity . There were also no differences in early mortality, relapse and long-term survival . We conclude that amifostine, while reducing the duration of mucositis and infections (possibly through some preservation of gut mucosal integrity), has a modest effect in allogeneic bone marrow transplants given the multiplicity of factors influencing organ toxicity and survival in this setting. Plant Physiol, 2004 Jun, 135(2), 709 - 14 Fluorescent screening of transgenic Arabidopsis seeds without germination; Wei S et al.; In this paper, we describe a reliable method for the screening and selection of Arabidopsis transgenic seeds within minutes without germination . Expression of the Aspergillus niger beta-glucosidase gene BGL1 in the plant's endoplasmic reticulum was used as a visual marker, together with 4-methylumbelliferyl-beta-D-glucopyranoside (MUGluc) as a substrate . Subsequent to incubation in a solution of MUGluc at room temperature for 2 to 15 min, transgenic seeds expressing BGL1 demonstrated a distinct fluorescent signal under UV light . Optimal screening conditions at room temperature were achieved between 75 and 450 microm MUGluc, at a pH of 2.5 to 5.0 and 2 to 5 min of incubation . No significant loss of viability was detected in transgenic seeds that were redried and stored for 45 d after incubation in MUGluc solution for 2 to 150 min . Transgenic plants expressing BGL1 displayed normal phenotypes relative to the wild type . Selection frequency was 3.1% +/- 0.34% for the fluorescence selection method, while kanamycin resistant selection resulted in only 0.56% +/- 0.13% using the same seed batch . This novel selection method is nondestructive, practical, and efficient, and eliminates the use of antibiotic genes . In addition, the procedure shortens the selection time from weeks to minutes. Emerg Med J, 2004 Jul, 21(4), 446 - 8 Limited usefulness of initial blood cultures in community acquired pneumonia; Corbo J et al.; OBJECTIVE: The incidence of community acquired pneumonia (CAP) is about 4 million cases per year, with a hospitalisation rate of 20% . In non-immunocompromised patients hospitalised for CAP the rate of bacteraemia is less than 7% with predictable pathogens . Despite this, guidelines still recommend use of blood cultures (BCs) to direct treatment . This study tested the primary hypothesis that the proportion of false positive BCs would exceed the proportion of true positives . A secondary aim was to quantify the frequency with which antibiotic therapy was changed based on BC results . METHOD: Consecutive adults hospitalised from an urban emergency department (ED) with CAP between January 1999 and March 2001 were assessed retrospectively for study eligibility . Those with an infiltrate consistent with pneumonia on the admission chest radiograph and at least one set of BCs taken in the ED before antibiotics were given were entered into the study . Patients hospitalised within the previous two weeks, nursing home residents, and immunosuppressed patients were excluded . RESULTS: 821 patients were admitted for CAP and 355 met inclusion criteria . The proportion of false positive BCs (10%) exceeded the proportion of true positives (9%), by 1% (95%CI -3.3% to 5.5%) . Antibiotic therapy was changed on the basis of BC results in 5% of patients (95%CI 3% to 8%) . CONCLUSION: The rate of false positive BCs in patients hospitalised with CAP is similar to the rate of true positives . BCs only infrequently lead to changes in antibiotic therapy, and in no instance were therapeutic changes driven by detection of resistant organisms . The results question the utility of routine BCs in immunocompetent patients with CAP. Enferm Infecc Microbiol Clin, 2004 May, 22(5), 279 - 85 {Indications for antifungal treatment in intensive care unit patients}; Alvarez-Lerma F et al.; INTRODUCTION: This study investigates the indications for antifungal treatment in patients admitted to intensive care units (ICUs) in Spain and determines the frequency at which each individual drug is prescribed . METHODS: Observational, multicenter study including all patients admitted to 64 ICUs on 23 March, 22 June, and 16 November, 1999 . The use of antifungal agents and the criteria for indicating antifungal therapy were assessed . Patients were classified as colonized or infected by fungi . RESULTS: In 180 (11.5%) of the 1562 patients included in the study, 219 courses of treatment with antifungal agents were prescribed (antifungal therapy rate of 14 per 100 patients) . Fluconazole was the antifungal agent most frequently used, both in infected and colonized patients . The most common reasons for prescribing antifungal therapy were as follows: candiduria (21.9%), severe sepsis with no response to antibiotic therapy (19.6%), and evidence of fungi in two or more non-invasive sites (16.9%) . Candidemia was the reason for antifungal treatment in 17 (7.9%) cases . Proven fungal infections accounted for 21.1% of indications . Variables significantly associated with the use of antifungal agents included underlying disease, severity of illness according to the APACHE II score, chronic liver disease, solid tumor, immunosuppression, and organ transplantation . Significant extrinsic risk factors for antifungal therapy included treatment with corticoids, chemotherapy, mechanical ventilation, urgent and/or elective surgery, and previous use of antibiotics . CONCLUSIONS: A total of 11.5% of patients included in the study were given one or more treatment courses with antifungal agents . Antifungal treatment was prescribed in proved fungal infections in only 21.1% of cases . Fluconazole was the antifungal agent most frequently used. Eur J Ophthalmol, 2004 May-Jun, 14(3), 185 - 92 Repeated probing results in the treatment of congenital nasolacrimal duct obstruction; Singh Bhinder G et al.; PURPOSE: To assess the results of our protocol of repeated probing for the treatment of congenital nasolacrimal duct obstruction in various presentations . METHODS: A total of 1600 patients (1748 eyes) with congenital dacryocystitis (850 boys, 750 girls; age range, 1 month to 48 months {mean 16.54 +/- 12.21 months}) were included . Diagnosis was confirmed by history of tearing, crusting of lids, and a boggy swelling over inner canthal region, which on pressure ejected mucopurulent discharge through punctum . Antibiotic eye drops were instilled five times a day for a week in affected eyes after the mother pressed the sac area and cleaned the discharge . The cases that were not relieved were subjected to sequential probing dilating with an increasing diameter probe repeated in failed cases second and third times at 1-week interval . RESULTS: Medical treatment was effective in only 60 eyes (3.43%) . Probing and syringing achieved successful results in 790 eyes (100%) aged 1 month to 12 months; 330 eyes (99.40%) aged 12 months to 18 months; 200 eyes (98%) aged 18 months to 24 months; 150 eyes (95.24%) aged 24 months to 36 months; and 158 eyes (89.87%) aged 36 months to 48 months . The cure rate with first probing was 98.10%, second probing was 99.64%, and third probing was 100% . CONCLUSIONS: Our protocol of medical regime and early probing repeated two to three times was very effective in the treatment of nasolacrimal duct obstruction at all ages . A second and third probing was recommended after 1 week of the first probing with successful results if first probing failed. Gen Dent, 2004 May-Jun, 52(3), 244 - 7 Tongue piercing: case report and ethical overview; Dunn WJ et al.; A case of infection following piercing of the tongue is presented . A dentist allegedly provided local anesthesia to the tongue prior to piercing . To avoid criticism from the first dentist, the patient saw a different dentist to treat the infection . The patient had symptoms of pain, inflammation, purulence, salivary incontinence, and difficulty speaking and swallowing . The ornament was discarded and the infection was resolved with antibiotic therapy . Ethical issues of administering anesthesia prior to piercing also are discussed. Arch Gynecol Obstet, 2004 May, 269(4), 233 - 6 Epub 2003 Dec 19. Granulomatous mastitis; Diesing D et al.; INTRODUCTION: Granulomatous mastitis (GM) is a rare disease which predominantly occurs in premenopausal women shortly after their last childbirth . ETIOLOGY: Its etiology is unclear, however, the disease has been shown to be correlated with breast-feeding and the use of oral contraceptives . An autoimmune component has also been discussed . PRESENTATION: It presents with the clinical symptoms of galactorrhea, inflammation, breast mass, tumorous indurations and ulcerations of the skin . In mammography and sonography nodular opacities and hypoechoic nodules are found . Very often clinical and radiological findings mimic breast cancer . HISTOLOGICAL DIAGNOSIS: The diagnosis is made by histopathology . Histological features in GM include signs of a chronic granulomatous inflammation with giant cells, leucocytes, epitheloid cells and macrophages as well as abscesses . TREATMENT: Therapy of GM consists of complete surgical excision combined with oral steroid therapy, eventually in combination with anti-inflammatory drugs or colchicine . Use of methotrexate has also been successful . In case of formation of abscesses antibiotic therapy should be applied before steroid therapy . Immune-suppressive therapy should be performed until complete remission as rates of recurrence can be up to 50%. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz, 2004 Apr, 47(4), 313 - 22 {1974-2004: the Commission for Hospital Hygiene has been working for 30 years . From the "old" to the "new" guideline}; Exner M et al.; After 2 years of preparation, the Commission for Hospital Hygiene, founded in 1974 by the former German Public Health Service, published the "Guideline for Assessment,Prevention, and Controlling of Nosocomial Infections," which represented an exemplarily complete standard for hospital hygiene . In 1997 within the framework of planning the amendment to the Federal Epidemic Law, a new Commission for Hygiene and Infectious Disease Prevention started work and adapted the guideline to meet today's standards of systematic risk analysis and risk management . The amended Infection Protection Act (Infektionsschutzgesetz, IfSG), which came into force in January 2001, installed the Commission for Hospital Hygiene and Infectious Disease Prevention legally and required it to formulate a guideline to decrease the rate of nosocomial infections, the number of outbreaks, and the dissemination of antibiotic-resistant pathogens in healthcare facilities by establishing standards of modern prevention . This article describes the political importance of nosocomial infections for public health as well as the working basis, the methods, and the latest guidelines of the Commission. Cytotherapy, 2004, 6(3), 183 - 95 Comparison of automated culture systems with a CFR/USP-compliant method for sterility testing of cell-therapy products; Khuu HM et al.; BACKGROUND: Although widely used, commercially available automated culture methods are not US Food and Drug Administration-approved for sterility testing of cell-therapy products . For cell-therapy products regulated under Section 351 of the Public Health Service Act, sterility testing must be performed by the methods described in 21 CFR 610.12 and USP <71> (CFR/USP method), or by methods demonstrated to be equivalent . METHODS: Two automated methods, BacT/Alert (BTA; bioMerieux) and Bactec (Becton Dickinson), were compared with the CFR/USP method . Representative mononuclear cell (MNC) products were formulated using six different product media . MNC product aliquots containing 10-50 x 10(6) cells in a 0.5 mL volume were seeded with organisms, and cultured for 14 days in aerobic and anaerobic bottles of each system . Ten different organisms at target concentrations of 10 and 50 colony-forming units (CFU) per bottle were tested . RESULTS: Positives were detected in a mean (range) of 72% (7-100%) of cultures for CFR/USP, 82% (0-100%) for BTA, and 93% (57-100%) for Bactec . For nine of the 10 organisms tested, overall detection rates for BTA and Bactec were equivalent to or higher than CFR/USP . Of the six product media tested, detection of organisms was impaired only by the medium containing multiple antibiotics: this occurred in all three systems . Both BTA and Bactec had shorter times to detection than the CFR/USP method, with overall means (ranges) of 87 (24-264) h for CFR/USP, 24 (12-54) h for BTA, and 33 (12-80) h for Bactec . Detection occurred consistently within 7 days for both BTA and Bactec, but not for CFR/USP . DISCUSSION: Both BTA and Bactec are superior to the CFR/USP method for overall detection and time to detection of organisms in MNC products suspended in commonly used media . These data support general use of either BTA or Bactec for sterility testing of a variety of cell-therapy products, and suggest that a 7-day culture period is sufficient to detect clinically relevant organisms . These results confirm the need for bacteriostasis and fungistasis testing of antibiotic-containing products, even when antibiotic-binding substances are used. J Org Chem, 2004 Jun 25, 69(13), 4446 - 53 Synthesis and conformational analysis of 1-{2,4-dideoxy-4-C-hydroxymethyl-alpha-l-lyxopyranosyl}thymine; Vanheusden V et al.; Previously different types of nucleosides with a six-membered carbohydrate moiety have been evaluated for their potential antiviral and antibiotic properties and as building blocks in nucleic acid synthesis . However, a pyranose nucleoside with a 1,4-substitution pattern like 1-{2,4-dideoxy-4-C-hydroxymethyl-alpha-l-lyxopyranosyl}thymine (4) has not been studied yet . Modeling suggested that this nucleoside would show the (4)C(1) conformation in contrast to anhydrohexitol nucleosides (1) whose most stable conformation is (1)C(4) . The key to the synthesis of 4 involves the stereoselective introduction of the hydroxymethyl group onto the C-4 carbon of the pyranose sugar . Attempts to achieve this via hydroboration/oxidation of a C-4'-exocyclic vinylic intermediate selectively yielded the undesired alpha-directed hydroxymethyl group . Therefore, we envisaged another approach in which the C-4 substituent was introduced upon treatment of 2,3-O-isopropylidene-1-O-methyl-4-O-phenoxythiocarbonyl-alpha-l-lyxopyranose with beta-tributylstannyl styrene . This allowed stereoselective beta-directed introduction of a 2-phenylethenyl group at C-4, which was converted via oxidation/reduction (OsO(4), NaIO(4)/NaBH(4)) into the desired 4-hydroxymethyl group (20) . The resulting 1-O-methyl-2,3,6-tri-O-acetyl-protected sugar was coupled with silylated thymine, using SnCl(2) as Lewis acid (22) . After suitable protection, Barton deoxygenation of the 2'-hydroxyl function of the obtained ribo-nucleoside yielded the desired 2'-deoxynucleoside 4, indeed showing the expected equatorial orientation of the thymine ring ((4)C(1)). Neurosurg Focus . 2004 Jun 15;16(6):ECP1. Iatrogenic spondylodiscitis . Case report and review of literature; Tasdemiroglu E et al.; Iatrogenic intervertebral disc space infection is encountered following microsurgical discectomy, percutaneous laser disc decompression, automated percutaneous lumbar nucleotomy operations, and discography . The purpose of this paper is to present a case report and review the literature on the uncommon origins of pyogenic spondylodiscitis and to emphasize the significance of prophylactic antibiotic therapy following transrectal ultrasonography-guided needle biopsy of the prostate (TUGNBP) . According to the authors, this is the first reported case of pyogenic spondylodiscitis as a complication of TUGNBP in the English language literature. Rev Esp Quimioter, 2004 Mar, 17(1), 57 - 63 {Levofloxacin in patients in the ICU . Factors influencing the choice of dose and its use in combined therapy}; Alvarez Lerma F et al.; This study aimed to identify factors that influence the selection of different approaches to prescribing levofloxacin (e.g., monotherapy vs . combined therapy, 12-h vs . 24-h interval) and the effect on mortality in the ICU . An observational, prospective, multicenter study was conducted . A logistic regression analysis was performed to identify factors associated with the prescription of levofloxacin in combined therapy and at a dose of 500 mg every 12 hours . In addition, a logistic regression analysis was conducted to determine the impact of the different prescribing methods on mortality in the ICU . The most frequently administered initial dose was 500 mg/24 h (48.5%) and 500 mg/12 h (48.3%) . No factors were found to influence the choice of daily dose . A total of 49.7% of levofloxacin prescriptions were in combined therapy . Factors influencing the decision to prescribe a combined regimen included diagnosis of extra-ICU nosocomial infection (OR: 1.97; 95% CI: 1.13-3.42); severe sepsis (OR: 2.56; 95% CI: 1.66-3.94); septic shock (OR: 6.22; 95% CI: 3.54-10.9); and identification of the causative pathogen (OR: 1.99: 95% CI: 1.34-2.95) . The mortality rate was 21.4% and the related factors were septic shock (OR: 3.09; 95% CI: 1.38-6.91); treatment failure (OR: 23.4; 95% CI: 12.3-44.6); and combined therapy (OR: 2.36; 95% CI: 1.21-4.59) . The selection of the initial dose of levofloxacin was not influenced by any factor, as long as the antibiotic was given in combined therapy in patients in whom the cause of the infection had been identified, in patients with greater systemic response, and in nosocomial infection outside the ICU . The selection of combined therapy was associated with a worse prognosis. Obstet Gynecol Clin North Am, 2004 Jun, 31(2), 429 - 59, viii Cardiac disease in pregnancy; Klein LL et al.; This article reviews the complications, management and prognosis of cardiac disease in pregnancy. Zhonghua Liu Xing Bing Xue Za Zhi, 2004 Mar, 25(3), 261 - 4 {A case-control study on risk factors of hypospadias}; Wang JP et al.; OBJECTIVE: Hypospadias is one of the most commonly seen urogenital congenital malformations in males and to identify its etiological factors . METHODS: A hospital-based case-control study was conducted, with 107 hypospadias cases . Two matched controls per case were randomly selected . Both cases and controls were face to face interviewed with a uniformed questionnaire . Conditional logistic regression model was used for univariable and multivariate analysis on SAS 6.12 to estimate odds ratios (OR) and 95 per cent confidence internals (95% CI) . RESULTS: Data from multiple conditional logistic regression analysis showed that hypospadias was positively associated with maternal history of spontaneous abortion (OR = 3.87, 95% CI: 1.60 - 9.39), with threatened abortion in the first or second trimester (OR = 3.57, 95% CI: 1.31 - 9.64), with common cold accompanied fever in the first trimester (OR = 7.63, 95% CI: 2.50 - 23.24), with maternal drug (antibiotic, analgesiscs) exposure during the second trimester (OR = 16.46, 95% CI: 3.46 - 78.21), with paternal exposure to pesticides occupationally (OR = 3.70,95% CI: 1.49 - 9.16), with neonatal low birth weight (OR = 12.62, 95% CI: 2.97 - 53.67), but was negatively associated with maternal diet supplemented with protein in the first trimester (OR = 0.33, 95% CI: 0.15 - 0.74) . CONCLUSIONS: The risk factors of hypospadias seemed to include maternal history of spontaneous abortion, threatened abortion in the first or second trimester, maternal common cold accompanied fever in the first trimester, maternal drug exposure during the second trimester, paternal occupational exposure to pesticides, neonatal low birth weight . However, maternal diet supplemented with protein probably acted as the protective factor for neonatal hypospadias in the first trimester. Ir Med J, 2004 Apr, 97(4), 108 - 10 Managing exacerbations of COPD: room for improvement; Butler MW et al.; Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a major cause of hospital admissions . Because of the consequent morbidity, mortality and burden on hospital resources, COPD management guidelines have been formulated . We reviewed 62 consecutive patients with AECOPD admitted from September 1st to December 18th 2000 in St . Vincents University Hospital, Ireland, including 3 months follow-up data, to evaluate the quality of care and in particular to assess the care of such patients by respiratory and non-respiratory physicians . There was a frequent failure to objectively confirm the diagnosis of COPD by spirometry (completed in 39 of the 51 patients who, at admission, had been previously labelled with COPD (76%), and in 53 out of 62 patients (85%) at the end of the study period), or to estimate severity by quantifying the FEV1 as a percentage of the normal predicted range (estimated in only 21 of the 39 patients who had spirometry previously performed (53%)) . Those patients managed with input from respiratory physicians were more likely to have their diagnosis of COPD confirmed with spirometry (p < 0.05) . They were also more likely to have out-patient follow-up arranged at discharge (p < 0.05) . There was a trend towards the more frequent prescribing of oxygen to hypoxic patients in "respiratory" than in "non-respiratory" managed cases (p = 0.182) and a shorter hospital stay (0.1 < p < 0.5) . 4 out of 11 severely hypoxaemic patients at admission (PO2 < 7.3kPa) were not screened at discharge for possible long term oxygen therapy (36%) . 20 patients received combination antibiotic therapy with no infiltrate on CXR (32%) . Pulmonary rehabilitation was offered to 12 patients (19%) . 5 out of 18 current smokers had documented smoking cessation advice (28%) and none received smoking cessation pharmacotherapy . Finally we noted that the Hospital In-Patient Enquiry (HIPE) data and casualty department admission books were frequently misleading or medical records unlocatable (in 30 out of 92 cases (33%)) . We conclude that the management of AECOPD at St . Vincent's University Hospital is frequently suboptimal, and may be managed better with respiratory physician involvement . In particular, there could be more frequent spirometric confirmation of the diagnosis of COPD, better screening for long term oxygen therapy and more conservative use of antibiotics . Audit is complicated by difficulty accessing relevant data. Immunol Rev, 2004 Apr, 198, 267 - 84 Metabolic reprogramming in plant innate immunity: the contributions of phenylpropanoid and oxylipin pathways; La Camera S et al.; In their environment, plants interact with a multitude of living organisms and have to cope with a large variety of aggressions of biotic or abiotic origin . To survive, plants have acquired, during evolution, complex mechanisms to detect their aggressors and defend themselves . Receptors and signaling pathways that are involved in such interactions with the environment are just beginning to be uncovered . What has been known for several decades is the extraordinary variety of chemical compounds the plants are capable to synthesize, and many of these products are implicated in defense responses . The number of natural products occurring in plants may be estimated in the range of hundreds of thousands, but only a fraction have been fully characterized . Despite the great importance of these metabolites for plant and also for human health, our knowledge about their biosynthetic pathways and functions is still fragmentary . Recent progress has been made particularly for phenylpropanoid and oxylipin metabolism, which are emphasized in this review . Both pathways are involved in plant resistance at several levels: by providing building units of physical barriers against pathogen invasion, by synthesizing an array of antibiotic compounds, and by producing signals implicated in the mounting of plant resistance. J Biomed Mater Res, 2004 Jul 15, 70B(1), 103 - 5 Release of anthracyclines adsorbed on copper-treated hydroxylapatites; Bacha RA et al.; Anthracyclines are antibiotics widely used for the treatment of leukemia and solid tumors . Perfusion is the standard clinical administration form . Unfortunately, this does not allow treatment of gastric cancers . A new galenic presentation, consisting of anthracyclines adsorbed onto hydroxylapatite granules, has been developed . It was found to be possible to modulate the release of the drug as a function of the pH by using copper(II) ions . At neutral pH, the drug remains on the mineral support, but at pH 3, the drug is released into solution . Further investigations demonstrate that copper-containing hydroxylapatite can retain a determined quantity of antibiotic by surface complexation . This result could contribute to new designs for drug carriers targeted for gastric cancers . Scand J Infect Dis, 2004, 36(4), 312 - 4 Two case reports: fatal Absidia corymbifera pulmonary tract infection in the first postoperative phase of a lung transplant patient receiving voriconazole prophylaxis, and transient bronchial Absidia corymbifera colonization in a lung transplant patient; Mattner F et al.; Absidia corymbifera is a rare cause of pulmonary tract infection . There exist only 5 case reports predominantly diagnosed in bone marrow transplant patients . Lung transplant patients are at high risk for invasive fungal infections . Due to A . corymbifera as pathogen, known to be voriconazole resistant, a fatal invasive pulmonary mycosis occurred . In the present case voriconazole prophylaxis failed . A second patient showed a transient colonization of the bronchi . To prevent airborne transmitted invasive pulmonary mycosis in the first postoperative period of lung transplantation the patient should be situated in a room ventilated by HEPA-filtered air . The specific treatment should start very early when first suspicion arises . A review of the literature on pulmonary tract infections induced by Absidia corymbifera is provided. Support Care Cancer, 2004 Aug, 12(8), 555 - 60 Epub 2004 Jun 09. Febrile neutropenia: a prospective study to validate the Multinational Association of Supportive Care of Cancer (MASCC) risk-index score; Uys A et al.; OBJECTIVE: The objective of this study was to prospectively validate the Multinational Association of Supportive Care of Cancer (MASCC) risk-index score in an attempt to accurately predict on presentation with febrile neutropenia those cancer patients who are at low- or high-risk for development of serious medical complications during the episode . PATIENTS AND METHODS: Patients who presented with febrile neutropenia during November 2000 and July 2002 were prospectively enrolled in the protocol . All patients were hospitalized until recovery or outcome of the event and were treated with broad-spectrum, empiric, intravenous antibiotic therapy . The MASCC risk-index score (based on seven independent factors present at onset of febrile neutropenia) was calculated in 64 patients with 80 febrile neutropenic episodes . Patients with a score of > or =21 were regarded as low risk; patients with a score of <21 were regarded as high risk . RESULTS: Of the 80 febrile neutropenic episodes, 58 were classified as low-risk and 22 as high-risk patients . Fifty-seven (98.3%) of the 58 low-risk patients recovered without complications, and three (13.6%) of the 22 high-risk patients did not develop medical complications . One low-risk patient developed a fungal infection but recovered completely in comparison to 11 high-risk patients (50%) who developed serious medical complications ( p<0.001) . None of the low-risk patients died . However, eight (36.4%) of the 22 high-risk patients died during the febrile neutropenic episode ( p<0.001), six as a consequence of sepsis and two due to rapidly uncontrolled cancer . CONCLUSION: We correctly predicted 98.3% of low-risk patients and 86.3% of high-risk patients . This study had a positive predictive value of 98.3% and a negative predictive value of 86.4% with both a sensitivity and specificity of 95% . The MASCC risk-index score correctly identifies low- and high-risk patients at presentation with febrile neutropenia. Arch Surg, 2004 Jun, 139(6), 603 - 7; discussion 607-8 Early experience with balloon brachytherapy for breast cancer; Dowlatshahi K et al.; HYPOTHESIS: Partial-breast irradiation for carcinoma by a single source of radiation placed in the center of a balloon inserted in the lumpectomy cavity is an effective method of treating breast cancer . Previous interstitial radiation therapy using iridium seeds placed within multiple catheters has been shown to be effective but impractical and cosmetically unacceptable to women . DESIGN: Prospective registry study . SETTING: Three university and community hospitals . PATIENTS: Women 40 years and older with histologically diagnosed in situ and invasive T1 through T2 and N0 or N1 breast cancer treated with lumpectomy and axillary node sampling were invited to enter this institutional review board-approved study . MAIN OUTCOME MEASURES: Evaluation of immediate and short-term complications, patients' acceptance of the treatment, and cosmesis are reported . RESULTS: Of the 129 eligible patients enrolled, 112 completed the treatment . Of these, transient skin erythema was noted in 28, localized edema in 3, and skin blisters adjacent to the balloon in 9 . Infection developed in 7, necessitating drainage and antibiotic administration . In 10 patients, sonographically demonstrated seromas that developed after removal of the device were aspirated percutaneously . In 4 patients, punctured or ruptured balloons had to be replaced before the treatment could be completed . Patients quickly adjusted to the breast distension caused by the balloon, and their acceptance of the procedure was good . The cosmetic outcome was rated high . There were no recurrences during this very short follow-up . CONCLUSIONS: Our early short-term experience indicates balloon brachytherapy to be an acceptable alternative to external beam radiation for selected operable breast cancers . The 1-week treatment time allows working women and those who live at a distance from radiation centers to choose breast conservation rather than mastectomy. Crit Care, 2004, 8 Suppl 2, S27 - 30 Epub 2004 Jun 14. To filter blood or universal leukoreduction: what is the answer? Shapiro MJ. The safety of the blood supply has been a concern over the past 20-30 years because of the transmission of infectious diseases . Blood is still routinely tested for viruses, and leukoreduction is an effective strategy to reduce the transmission of cell-associated viruses . Clinically, the benefits of leukoreduction include decreases in transfusion reactions, HLA alloimmunization, infections, fever episodes, and antibiotic use . Although leukoreduction will add cost to a unit of blood, projections indicate that leukoreduced blood will become the standard of care. Arch Environ Contam Toxicol, 2004 Apr, 46(3), 289 - 95 A procedure to purify and culture a clonal strain of the aquatic moss Fontinalis antipyretica for use as a bioindicator of heavy metals; Rausch de Traubenberg C et al.; A procedure to culture the aquatic moss, Fontinalis antipyretica, is described . The moss was collected in a stream, carried to the laboratory, and immediately treated: apices were isolated and rinsed under a stereomicroscope and submitted to ultrasonic cleaning combined with an iodine treatment and then to an antibiotic/anti-eukaryotic treatment for 4 days . This procedure permitted us for the first time to eliminate the microalgae associated with an aquatic moss in culture, solving the problem of proliferation of these microalgae in the culture medium . Furthermore, the minimal concentration of eight essential metals required by this moss was determined in order to have metal concentrations in the cultured moss as low as possible . A perennial culture of a clonal strain of an aquatic moss for use as a metal bioaccumulator was obtained and the first step to provide a standardized bioindication tool for metal detection in continental waters was passed over. Zhonghua Er Bi Yan Hou Ke Za Zhi, 2004 Feb, 39(2), 112 - 5 {Effect of specific immunoglobulin Y in the treatment of acute and chronic pharyngitis}; Xie MQ et al.; OBJECTIVE: To evaluate the effect and safety of the specific immunoglobulin Y (IgY) for treatment of acute and chronic pharyngitis . METHODS: Double-blind, randomized, placebo-controlled trial was conducted on 50 adults with acute pharyngitis . Experimental group received a 6 times-daily total 30 doses of IgY stomat-spray which contained specific immunoglobulin Y (titer = 512) prepared from the egg yolk of hens immunized with a variety of bacteria . Another open label trial included 50 patients, whose ages ranged from 21-69 years, including 25 cases of acute pharyngitis and 25 cases of chronic pharyngitis were also treated using IgY stomat-spray . The therapeutic effect were objectively evaluated 7 days later by the decreased scores based on both the symptoms and physical signs . If the symptom did not improve or became severe three days later, these patients with acute pharyngitis was inefficiency and antibiotic medicine would be added to them . RESULTS: In Double-blind trial, 8 cases (32%) received IgY had apparent effect with the decreased scores 5 or more than 5, 13 cases (52%) had effective with the decreased scores 3-4, and other 4 cases (16%) had inefficacy with the decreased scores only 2 or no more than 2 . While in placebo-controlled group, only 2 (8%) cases had apparent effect, 5 (20%) cases showed effective and 18 (72%) cases had non-effect . The difference between the two groups was significant (chi 2 = 16.06, P < 0.01) . In open label trial, 19 cases (38%) showed apparent effect, in which 14 cases were acute pharygitis . 23 cases (46%) had effective, in which 10 cases were acute pharyngitis . The left 8 cases (16%) had ineffective, in which one case was acute pharyngitis . There was significantly difference (chi 2 = 8.90, P < 0.05) between acute pharyngitis and chronic pharyngitis . An average of three months followup showed that there were no side effect or toxic effect and no allergic reaction . CONCLUSION: The IgY stomat-spray is a safe and effective agent in treating acute and chronic pharyngitis, especially for acute pharyngitis. Neuroreport, 2004 Jun 28, 15(9), 1379 - 82 Medial olivocochlear efferent activity in awake guinea pigs; Guitton MJ et al.; Cochlear outer hair cells receive numerous connections from the medial olivocochlear efferent neurons . Medial olivocochlear efferent activity is highly dependent on the level of anesthesia . The present study was thus designed to investigate the efficiency of contralateral white noise stimulation on the distortion product otoacoustic emissions (DPOAEs) in a large number of awake guinea pigs, and to compare in the same animals the effect of urethane- and pentobarbitone-anesthesia . The monitoring of DPOAEs during contralateral white noise stimulation in awake animals requires the development of a soft restraining box, together with a conditioning technique for the animals to accept the contralateral sound and DPOAEs monitoring device . This technique allows us to demonstrate that contralateral sound suppression is much stronger in awake than in anesthetized animals . In all the cases, the contralateral sound suppression was abolished 3 h after i.m . injection of gentamicin, an aminoglycoside antibiotic which blocks the medial olivocochlear efferents . These results suggest that future studies have to explore the function of medial olivocochlear efferents in awake animals. Pediatr Infect Dis J, 2004 Jun, 23(6), 590 - 1 Mycobacterium bovis versus Mycobacterium tuberculosis as a cause of acute cervical lymphadenitis without pulmonary disease; Fennelly GJ; Bovine tuberculosis remains a common disease of cattle in countries such as Mexico . Children eating unpasteurized dairy products from Mexican cattle can develop Mycobacterium bovis cervical lymphadenitis . However, the bovine mycobacterium can be misdiagnosed as Mycobacterium tuberculosis based on standard laboratory testing . Accurate speciation is important for selection of the preferred antibiotic regimen for treatment of Mycobacterium bovis infection. J Am Coll Surg, 2004 Jun, 198(6), 877 - 83 Outcomes and prediction of hospital readmission after intestinal surgery; Kiran RP et al.; BACKGROUND: Clinical care pathways reduce postoperative stay after major bowel operations . Concerns about unexpected early readmissions and delays in diagnosis of complications remain unanswered . The objectives of this study were determination of readmission rate and outcomes for patients undergoing intestinal operations . STUDY DESIGN: Patients readmitted (PR) within 30 days of discharge after intestinal operations were compared with patients who were not readmitted (NR) . Variables that might predict readmission were evaluated . RESULTS: Of 553 patients, 56 (10.1%) were readmitted after 10 days (interquartile range {IQR} 4.5 to 15.5 days) . PR and NR groups had similar age, gender, diagnosis, preoperative comorbidities, and index operations . Discharge hemoglobin level, white cell count, antibiotic use, or presence of stoma did not affect readmission . PR had a greater frequency of steroid use (p = 0.03) during index admission . Median length of stay for the index hospitalization was 5 days (IQR 4 to 8 days) for the NR and 6 days (IQR 4.8 to 9 days) for the PR group (p = 0.049) . Duration of readmission was 4 days (IQR 2 to 9 days) in the PR group, with equal total median length of stay identical for PR and NR patients with complications (median 12 days) . Clinical outcomes for PR patients and NR patients with complications were similar . CONCLUSIONS: Early readmission is an unpredictable sequel of major bowel operations; it does not correlate with shorter hospital stay . Identification of unpredictable complications after discharge that require later invasive intervention does not adversely affect clinical outcomes . Readmission within 30 days of a patient who has attained standardized discharge criteria may not be a valid indicator of poor quality of care. Med Hypotheses, 2004, 63(1), 31 - 4 Why minocycline can cause systemic lupus - a hypothesis and suggestions for therapeutic interventions based on it; van Steensel MA; The tetracycline antibiotic minocycline is widely used in dermatology, but can sometimes cause systemic lupus erythematodes, a serious autoimmune disorder . It is not known how it does this . However, recent data suggest that minocycline can protect cells from apoptosis by inhibition of caspase-dependent and independent cell death pathways . Here, it is suggested that this ability of minocycline is responsible for the induction of lupus . This idea is based on the recent insight that incomplete or failed apoptosis of damaged cells, particularly keratinocytes, may be responsible for the development of auto-immunity . The protection against apoptosis as conferred by minocyclin may be incomplete, with failed apoptosis and development of autoimmunity as a result . Experimental confirmation of the theory may be obtained by in vitro experiments using induction of apoptosis in cell types known to be affected by lupus . Next, mice that are sensitive to apoptosis may be used for in vivo experiments . Novel therapeutic approaches to drug-induced lupus may be based on induction of apoptosis; DNA-damaging immunosuppressive agents appear particularly useful . Such treatments can be tested in apoptosis-deficient mice that develop autoimmune disease. Apoptosis, 2004 Jul, 9(4), 429 - 35 Characterization of 4-O-methyl-ascochlorin-induced apoptosis in comparison with typical apoptotic inducers in human leukemia cell lines; Tsuruga M et al.; Apoptosis can be induced by various stimuli such as the ligands of death receptors, chemotherapeutic drugs and irradiation . It is generally believed that chemotherapeutic drugs induce mitochondrial damage, cytochrome c release and activation of caspase-9, leading to apoptosis . Here, we found that an isoprenoid antibiotic, 4-O-methyl ascochlorin, significantly induces typical apoptotic events in Jurkat cells including the degradation of poly (ADP-ribose) polymerase, DNA fragmentation, activation of caspase-3, -9 and -8, and cytochrome c release from mitochondria . Similar to Fas stimulation, 4-O-methyl ascochlorin but not staurosporine, cycloheximide and actinomycin D, induced apoptosis in SKW6.4 cells, in which apoptosis is strongly dependent on death-inducing signaling-complex . Bcl-2 overexpression in Jurkat cells completely suppressed the apoptosis, but procaspase-9 processing was partially induced . A caspase-8 inhibitor, IETD-fmk, effectively suppressed poly (ADP-ribose) polymerase cleavage and cytochrome c release . However, 4-O-methyl ascochlorin induced apoptosis in Jurkat cells deficient of caspase-8 or Fas-associated death domain protein . These results suggest that 4-O-methyl ascochlorin induces apoptosis through the mechanism distinct from conventional apoptosis inducers . Adv Ther, 2004 Jan-Feb, 21(1), 39 - 46 Serum IL-8 as a possible marker for determining the status of Helicobacter pylori infection in patients with untreated and treated peptic ulcer; Cheng KS et al.; Failure to eradicate Helicobacter pylori can lead to peptic ulcer recurrence and gastric malignancy . Therefore, the objective of this study was to develop a noninvasive method for determining whether H . pylori infection was eradicated with antibiotic-based triple therapy . A total of 17 patients with duodenal ulcer (DU) and 17 with gastric ulcer (GU) were evaluated both before and after treatment . Outcomes included serum levels of interleukin-8 (IL-8), pepsinogen I, and gastrin, and the Wilcoxon signed rank test was used to test significance . Changes in these parameters were also correlated with disease status . In those patients where both GU and DU healing occurred as a result of treatment, most showed an increase in serum IL-8 and a decrease in serum pepsinogen . Serum gastrin levels were not significantly changed in either group . Posttreatment increases in serum IL-8 were seen in 15 of 17 (88%) recovered DU patients and 14 of 17 (82%) recovered GU patients (P<.05 for each) . Posttreatment decreases in pepsinogen I were found in 15 of 17 DU and 15 of 17 GU patients (P<.05 for each) . These preliminary findings suggest that an increase in serum IL-8 and possibly a decrease in pepsinogen I may be useful in identifying the successful eradication of H . pylori infection in patients with peptic ulcer treated with antibiotics . A more systematic analysis of these putative diagnostic markers is now warranted. J Healthc Manag, 2004 May-Jun, 49(3), 199 - 205 Getting a return on investment from spending capital dollars on new beds; Hardy PA; In assessing this bed-purchase process and the resulting return on investment, I identified the following critical success factors related to capital investments: Evaluation of capital equipment for return on investment from the expense side, particularly when looking at use of manpower for critical positions in the organization Evaluation of capital equipment for increasing nursing satisfaction, a factor in addressing the healthcare worker shortage in today's environment Involvement of a representative team to create personal ownership through individuals wanting to take care of something they are involved in purchasing Spin-off timesaving that can be realized through the adage "form follows function" The last factor was found not only in savings of nurse staff time but also in pharmacy time because the weight function on the new beds saved approximately one hour, allowing for speedier calculation of creatinine clearance in antibiotic dosing . Changing my position and perspective was rewarding . The persistence of the CNO and the involvement of the employees made the experience gratifying on a personal level as well. Harefuah, 2004 May, 143(5), 377 - 81, 389 {An update on probiotics and prebiotics in children}; Shaoul R et al.; This review presents an update on the use of probiotics and prebiotics in children . We review the normal flora, and present the possible mechanisms by which the probiotic bacteria exert their beneficial effects . We present data from multiple studies suggesting that probiotics are effective for the treatment and prevention of acute non-bloody infections diarrhea, antibiotic associated diarrhea as well as the prevention and treatment of atopic dermatitis and other allergic conditions . The safety and future directions of pro- and prebiotic treatments are discussed. J Health Popul Nutr, 2004 Mar, 22(1), 46 - 51 Management of childhood febrile illness prior to clinic attendance in urban Nigeria; Afolabi BM et al.; Parents and caregivers often try various treatment modalities for their sick children before bringing them to clinic . Many community-based studies have documented home and self-treatment practices, often with the aid of patent medicine vendors, but less is known about prior treatment behaviour of caregivers who actually reach a government clinic . This study, therefore, aimed at documenting the treatment provided by caregivers prior to their attendance at a public hospital . Beginning in April 1996, a year-long study was conducted among 1,943 sick children and their caregivers who attended the largest government-owned paediatric hospital in Lagos, Nigeria . The major complaints mentioned by the caregivers included fever, cough, and diarrhoea . Most (89%) caregivers had administered some form of medicine to the child prior to the clinic visit, and on average, 2.5 medications had been given . Associations were found between major complaint and type of medicine given: fevers were associated with antimalarial drugs and analgesics (antipyretics), cough was associated with cough syrup and analgesics, while diarrhoea was associated with antidiarrhoeal drugs . Although one-fifth of the children had received an antibiotic, provision of antibiotics was not associated with a particular complaint/illness . Since caregivers appeared to use perceived complaints/illnesses as a treatment guide, this can form the basis of safer and more appropriate recognition of illness and home management . In addition, the information obtained in this study can be used for training clinicians to inquire about home management and, thus, for making more informed decisions about their own treatment and prescribing practices. Hua Xi Kou Qiang Yi Xue Za Zhi, 2004 Apr, 22(2), 96 - 9 {Transfection of human endostatin gene with lipofectamin and the expression of hES protein in Tca8113 cell}; Pan CB et al.; OBJECTIVE: The purpose of this study was to establish transfergeneic Tca8113 cell and evaluate the expression of human endostatin (hES) gene in the cell colone in vitro . METHODS: To transfect hES gene into Tca8113 cells, lipofectamin was complexed with plasmid encoding hES gene, and blasticidin S antibiotic was adopted to select Tca8113--hES cell clone . Immunohistochemistry S-P method was adopted to detect the expression of hES in the transfergenic Tca8113 cell in vitro . RESULTS: Transfected by hES, the transfergenic Tca8113 cells could grow and proliferate in RPMI--1640 culture medium containing blasticidin S antibiotic . The expression rate of hES reached 100% . CONCLUSION: hES gene can express in hES-transfected Tca8113 cell in vitro. Rev Port Pneumol, 2003 Nov-Dec, 9(6), 503 - 14 {Difficulties on diagnosis of ventilator associated pneumonia}; Machado MA et al.; Ventilator associated pneumonia is associated with high morbidity and mortality . It is important a correct diagnosis in way to guide the antibiotic therapy in the most appropriate way . However, its diagnosis is difficult, because clinical and radiologic features are not specific and approaches to standard diagnosis, that allow its confirmation, are very invasive or not very frequent . Protected techniques and quantitative cultures have been trying to outline the problem of the contamination of the samples obtained by routine methods and to allow the distinction between colonization and infection . The author makes a revision on the different methods of diagnosis of this clinical entity. Biophys J, 2004 Jun, 86(6), 3687 - 99 Peptaibol zervamicin IIb structure and dynamics refinement from transhydrogen bond J couplings; Shenkarev ZO et al.; Zervamicin IIB (Zrv-IIB) is a channel-forming peptaibol antibiotic of fungal origin . The measured transhydrogen bond (3h)J(NC') couplings in methanol solution heaving average value of -0.41 Hz indicate that the stability of the Zrv-IIB helix in this milieu is comparable to the stability of helices in globular proteins . The N-terminus of the peptide forms an alpha-helix, whereas 3(10)-helical hydrogen bonds stabilize the C-terminus . However, two weak transhydrogen bond peaks are observed in a long-range HNCO spectrum for HN Aib(12) . Energy calculations using the Empirical Conformation Energy Program for Peptides (ECEPP)/2 force field and the implicit solvent model show that the middle of the peptide helix accommodates a bifurcated hydrogen bond that is simultaneously formed between HN Aib(12) and CO Leu(8) and CO Aib(9) . Several lowered (3h)J(NC') on a polar face of the helix correlate with the conformational exchange process observed earlier and imply dynamic distortions of a hydrogen bond pattern with the predominant population of a properly folded helical structure . The refined structure of Zrv-IIB on the basis of the observed hydrogen bond pattern has a small ( approximately 20 degrees ) angle of helix bending that is virtually identical to the angle of bending in dodecylphosphocholine (DPC) micelles, indicating the stability of a hinge region in different environments . NMR parameters ((1)HN chemical shifts and transpeptide bond (1)J(NC') couplings) sensitive to hydrogen bonding along with the solvent accessible surface area of carbonyl oxygens indicate a large polar patch on the convex side of the helix formed by three exposed backbone carbonyls of Aib(7), Aib(9), and Hyp(10) and polar side chains of Hyp(10), Gln(11), and Hyp(13) . The unique structural features, high helix stability and the enhanced polar patch, set apart Zrv-IIB from other peptaibols (for example, alamethicin) and possibly underlie its biological and physiological properties. Infection, 2004 Jun, 32(3), 176 - 8 Trimethoprim-sulfamethoxazole exacerbates posthypoxic action myoclonus in a patient with suspicion of Pneumocystis jiroveci infection; Jundt F et al.; We describe a 58-year-old patient with relapsing high-grade non-Hodgkin's lymphoma who exhibited exacerbation of posthypoxic action myoclonus during high-dose intravenous trimethoprim-sulfamethoxazole (TMP-SMX) treatment for highly suspicious Pneumocystis jiroveci pneumonia (PCP) . Three months previously the patient had experienced a hypoxic insult caused by respiratory arrest due to an anaphylactic reaction to antibiotic therapy . He had developed posthypoxic action myoclonus (Lance-Adams syndrome), which was well controlled by oral treatment with piracetam . However, after TMP-SMX therapy (115 mg/kg daily) was started for suspicion of newly developed PCP, posthypoxic action myoclonus worsened dramatically resulting in complete disability . Anti-myoclonic therapy with increased doses of piracetam and valproic acid did not significantly improve his clinical condition . Only when TMPSMX doses were reduced (38 mg/kg daily) on day 12 did action myoclonus cease within 2 to 3 days . We suggest that TMP-SMX can exacerbate posthypoxic action myoclonus . Copyright Urban and Vogel An Otorrinolaringol Ibero Am, 2004, 31(2), 105 - 13 {Latero-pharyngeal phlegmons and abscesses in adults . Reports of 6 cases and literature review}; Pino Rivero V et al.; Lateropharyngeal phlegmons and abscesses are an uncommon complication actually but they are requiring an adequate knowledge to get later an adequate treatment . We are reporting a clinical review of 6 cases corresponding to adults admitted by our ENT service in 11 years period . Four were men and two women with ages between 21 and 92 years old . In most of them it was found a pharyngotonsillar focus and after the diagnosis they were treated by endovenous antibiotic therapy, corticoid and, in one case, surgery by incision and drainage . All the patients had a satisfactory evolution standing between 6-12 days in the hospital . We have performed a bibliographic review on this subject. Akush Ginekol (Sofiia), 2004, 43(2), 11 - 3 {Immunostimulation as a part of urologic infection therapy in pregnancy}; Nikolov A et al.; Twenty-six pregnant women (group I) with uroinfection were treated with Urostim and antibiotic . The effect of treatment was compared to that of 20 pregnant women (group II) treated with antibiotic only . In group I recurrence of infections was found out in 15.3%, while in group II in 55% . We would like to offer it as part of the treatment of uroinfections with pregnant women, because it will reduce the usage of antibiotics and the recurrence of the uroinfections in postpartum period. J Pediatr Surg, 2004 Jun, 39(6), 875 - 9; discussion 875-9 The management of pediatric appendicitis: a survey of North American Pediatric Surgeons; Muehlstedt SG et al.; BACKGROUND/PURPOSE: Variation exists among pediatric surgeons in the management of pediatric appendicitis . The goal of this study was to determine current practice patterns and provide a foundation for evidence-based outcome studies that would standardize patient care . METHODS: Members of the American Pediatric Surgical Association (APSA) were surveyed . Data included preference of imaging, timing of operation, and opinions on interval appendectomy . Intraoperative principles surveyed included use of cultures, antibiotic irrigation, transperitoneal drains, and method of wound closure . Spectrum and duration of antibiotic coverage were assessed, as were discharge criteria . RESULTS: Survey response was 70% . A majority prefers computerized tomographic (CT) imaging and favors interval appendectomy in appropriate candidates . Seventy percent indicate a stable child with suspected appendicitis would be operated on in a semiurgent manner rather than emergently in their practice . Discrepancy exists in the type and duration of antibiotic coverage, impact of clinical parameters on antibiotic use, and utility of discharge criteria . CONCLUSIONS: This study consolidates current opinions on appropriate management of pediatric appendicitis, providing a foundation for evidence-based outcome studies capable of bringing conformity to the management of this surgical disease . Such studies would establish clinical practice guidelines that optimize resource utilization while maintaining quality care. Appl Environ Microbiol, 2004 Jun, 70(6), 3733 - 5 Methods for enhanced culture recovery of Francisella tularensis; Petersen JM et al.; Francisella tularensis is found in a wide variety of hosts and extrahost environments, making culture recovery a diagnostic challenge . Here we demonstrate improved recovery times and good sensitivity (90%) when cultures were inoculated on the site of an investigation using fresh tissues . For contaminated specimens, antibiotic supplementation of enriched cysteine heart agar blood culture medium improved recovery of F . tularensis by 81.1% . For transport of tissues, immediate freezing yielded culture recovery rates as high as 94%. Urology, 2004 Jun, 63(6), 1182 - 3 Eosinophilic cystitis after bladder instillation with dimethyl sulfoxide; Abramov Y et al.; Eosinophilic cystitis is a rare and poorly understood disorder . We report the first case of an acute flare of eosinophilic cystitis in a 51-year-old woman after bladder instillation with dimethyl sulfoxide (DMSO) for presumed interstitial cystitis . The patient presented with severe bladder pain, fever, and eosinophilia several hours after instillation . These symptoms were unresponsive to conventional analgesic and antibiotic treatments . Cystoscopy revealed erythema and exudate at the bladder walls, along with edema of both ureteral orifices . Bladder biopsies demonstrated massive eosinophilic infiltration of the bladder, confirming the diagnosis of eosinophilic cystitis . Urologists should bear in mind this clinical entity, particularly when DMSO is administered to patients with multiple drug allergies. Urology, 2004 Jun, 63(6), 1017 - 20; discussion 1020 Three-dimensional ultrasound guidance for percutaneous drainage of prostatic abscesses; Varkarakis J et al.; OBJECTIVES: To evaluate the feasibility and effectiveness of three-dimensional ultrasound-guided transperineal puncture and drainage of prostatic abscesses . METHODS: Between 1985 and 2003, a prostatic abscess was diagnosed in 22 patients . One of the therapeutic modalities used to drain the abscesses was transperineal puncture under three-dimensional ultrasound guidance . The postoperative results were compared with the outcomes of other modalities . RESULTS: The average patient age was 52 years . Predisposing factors were present in 12 patients . Transperineal puncture was performed in 7 patients under general anesthesia . In addition to antibiotic therapy, a nephrostomy tube was left in place in all cases for a mean period of 3 days to drain the abscess . All patients were treated effectively without additional therapy or complications . CONCLUSIONS: Three-dimensional ultrasound-guided transperineal puncture is a minimally invasive and effective technique for the treatment of prostatic abscesses. Biomed Pharmacother, 2004 May, 58(4), 239 - 44 Artificial neural network modeling to predict the plasma concentration of aminoglycosides in burn patients; Yamamura S et al.; The goal was to use an artificial neural network model to predict the plasma concentration of aminoglycosides in burn patients and identify patients whose plasma antibiotic concentration would be sub-therapeutic based on the patients' physiological data and taking into account burn severity . Physiological data and some indicators of burn severity were collected from 30 burn patients who received arbekacin . A three-layer artificial neural network with five neurons in the hidden layer was used to predict the plasma concentration of arbekacin . Linear modeling for prediction of plasma concentration and logistic regression modeling for the classification of patients were also used and the predictive performance was compared to results from the artificial neural network model . Dose, body mass index, serum creatinine concentration and amount of parenteral fluid were selected as covariates for the plasma concentration of arbekacin . Area of burn after skin graft was a good covariate for indicating burn severity . Predictive performance of the artificial neural network model including burn severity was much better than linear modeling and logistic regression analysis . An artificial neural network model should be helpful for the prediction of plasma concentration using patients' physiological data, and burn severity should be included for improved prediction in burn patients . Because the relationship between burn severity and plasma concentration of aminoglycosides is thought to be nonlinear, it is not surprising that the artificial neural network model showed better predictive performance compared to the linear or logistic regression models. Can J Urol, 2004 Apr, 11(2), 2210 - 5 Posterior urethral valves in Eastern Ontario - a 30 year perspective; Warren J et al.; INTRODUCTION: Posterior urethral valves (PUV) are the most common cause of male pediatric obstructive uropathy . Recent advancements in antenatal ultrasound and endoscopy have altered the presentation and management of PUV . Herein we describe the presentation, management and outcome of PUV patients in Eastern Ontario/Western Quebec over the last 3 decades . A comparison analysis of those cases identified pre and post widespread utilization of antenatal ultrasound diagnosis was performed to discern the clinical evolution of PUV with respect to long-term outcome . METHODS: Retrospective systematic chart review of all PUV cases diagnosed and treated at the Children's Hospital of Eastern Ontario over the last 3 decades . Charts were reviewed for initial presentation, method of diagnosis, radiological and clinical findings at diagnosis, initial management, and long-term clinical outcome . The evolution of PUV was interpreted by dividing the cohort into two groups chronologically delineated by the first case detected by antenatal ultrasound in the mid-1980s . These pre- and post- antenatal ultrasound eras were compared with respect to the parameters outlined above . RESULTS: Fifty-three cases were reviewed - 21 prior to widespread antenatal ultrasound screening in the mid-1980s and 32 after . There were 13/53 cases (32%) discovered by prenatal ultrasound evidence of hydronephrosis, none prior to 1985 . VCUG confirmed the diagnosis in all cases . Mean age at presentation in the remaining post-natally diagnosed patients was 33 months . Of the cases diagnosed post-natally, ultrasound investigation complemented VCUG findings in 19/40 cases (47%), whereas IVP was utilized in 14/40 (35%) . IVP has not been utilized for this purpose since 1987 . Overall, 26/53 cases (49%) had documented VUR - 16/26 (62%) bilateral; 42/53 (79%) had hydronephrosis on ultrasound - 37/42 (88%) bilateral; 26/53 (49%) had radiological evidence of renal parenchymal damage at diagnosis; 41/53 (77%) cases had a thickened bladder wall on ultrasound at diagnosis, and 23/53 (43%) had at least one bladder diverticulum . Techniques of initial management comprised: valve ablation 32/53, vesicostomy 11/53, and high diversion 10/53 . Clinically significant bladder dysfunction was found in 31% of cases, ranging from bladder instability to myogenic failure . Globally impaired renal function, as determined by significantly elevated serum creatinine levels, reduced GFR, or both, was found in 12/53 (23%) . 6/53 (11%) progressed to ESRD, of which 4 received transplants . Two patients died - one from complications related to renal failure . Of the six cases of myogenic bladder failure identified, three (50%) had concurrently significant renal impairment . Average length of follow-up was 8.3 years, varying between 1 month and 18 years . CONCLUSIONS: The presentation of PUV is variable, and currently antenatal detection is the most common mode . Despite this, it still does not make up the majority of diagnoses . Complete radiological work up should include abdominal and pelvic U/S in conjunction with VCUG . Concurrent VUR in 50% of boys mandates suppressive antibiotic use . Primary valve ablation remains the gold standard for treatment of PUV, with vesicostomy reserved for selected cases . Long-term bladder and renal dysfunction is common in this population, and mandates long-term urological and nephrological follow-up. Cutis, 2004 May, 73(5 Suppl), 23 - 4 The dermatologist's role in managing skin and soft tissue infections; Zalar GL; Dermatologists are often the first point of care for patients with skin and soft tissue bacterial infections . First, physical examination and patient history are central points of assessment to determine severity of infection, pathogen involved, and appropriate course of action . As preexisting conditions may exert a role both in the etiology of an infection and in the choice of antibiotic therapy prescribed, the clinician must be aware of the right questions to ask to achieve a complete diagnostic picture . Finally, the clinician should have a good understanding of the drugs most appropriate for different pathogens and have clear expectations of how quickly the infection should respond to therapy. Arch Pharm Res, 2004 Apr, 27(4), 407 - 14 Histone deacetylase inhibitor stimulate CYP3A4 proximal promoter activity in HepG2 cells; Kim JY et al.; The expression of CYP3A4 gene is induced by a variety of structurally unrelated xenobiotics including the antibiotic rifampicin, pregnenolone 16-carbonitrile (PCN), and endogenous hormones, that might mediate through steroid and xenobiotic receptor (SXR) system . The molecular mechanisms underlying regulation of CYP3A4 gene expression have not been understood . In order to gain the insight of the molecular mechanism of CYP3A4 gene expression, study has been undertaken to investigate if the histone deacetylation is involved in the regulation of CYP3A4 gene expression by proximal promoter in human hepatoma HepG2 cells . Also we have investigated to see if SXR is involved in the regulation of CYP3A4 proximal promoter activity in human hepatoma HepG2 cells . HepG2 cells were transfected with a plasmid pCYP3A4-Luc containing approximately 1 kb of the CYP3A4 proximal promoter region (-863 to +64 bp) in front of a reporter gene, luciferase, in the presence or absence of pSAP-SXR . In HepG2 cells, CYP3A4 inducers, such as rifampicin, PCN and RU486 showed minimal stimulation of CYP3A4 proximal promoter activity in the absence of SXR and histone deacetylase (HDAC) inhibitors . 4-Dimethylamino-N-{4-(2-hydroxycarbamoylvinyl)benzyl}benzamide (IN2001), a new class HDAC inhibitor significantly increased CYP3A4 proximal promoter activity over untreated control cells and rifampicin concomitant treatment with IN2001 increased further CYP3A4 proximal promoter activity that was stimulated by IN2001 . The results of this study demonstrated that both HDAC inhibitors and SXR are essential to increase of CYP3A4 proximal promoter activity by CYP3A4 inducers such as PCN, rifampicin, and RU486 . Especially SXR seems to be important for the dose dependent response of CYP3A4 inducing chemicals to stimulate CYP3A4 proximal promoter activity . Also this data suggested that HDAC inhibitors seemed to facilitate the CYP3A4 proximal promoter to be activated by chemicals. Osaka City Med J, 2003 Dec, 49(2), 57 - 60 Intracystic hemorrhage with spontaneous rupture of liver cyst complicated by infection: a case report; Kanazawa A et al.; A 78-year-old man who was being followed-up for a liver cyst was admitted to Asakayama General Hospital because of the sudden onset of severe right hypochondralgia and fever, with a preceding dull pain in the right upper quadrant of the abdomen of four 'days' duration . Computed tomography revealed remarkable enlargement of the liver cyst . We diagnosed intracystic hemorrhage and spontaneous rupture of the liver cyst . As we diagnosed bacterial infection in the ruptured cyst, transhepatic cystic drainage was performed . After improving the clinical status of the patient, we injected ethanol into the cyst, inducing a significant decrease in its size . There has been a few previous reports of intracystic hemorrhage and spontaneous rupture of a liver cyst complicated by infection . Transhepatic cyst drainage combined with antibiotic therapy and intracystic ethanol injection may be a useful and minimally invasive method for liver cysts with these complications, especially in compromised patients. Clin Pharmacol Ther, 2004 Jun, 75(6), 516 - 28 CYP3A5 genotype has a dose-dependent effect on ABT-773 plasma levels; Katz DA et al.; BACKGROUND: The metabolizing enzyme cytochrome P450 (CYP) 3A5 is polymorphically expressed as a result of genetic variants that do not encode functional protein . Because of overlapping substrate specificity with CYP3A4 and the multidrug efflux pump P-glycoprotein, the importance of CYP3A5 genetic polymorphism for pharmacokinetics is controversial . OBJECTIVE: Our objective was to determine whether genetic polymorphisms in CYP3A5 or MDR-1 (which encodes P-glycoprotein) influence the drug levels of ABT-773, a ketolide antibiotic that is a substrate for both CYP3A and P-glycoprotein . METHODS: Healthy volunteers given 3 different oral dose levels of ABT-773 were genotyped at 2 common CYP3A5 and 7 common MDR-1 polymorphisms . Individuals were categorized as CYP3A5-positive if they carried at least 1 functional CYP3A5*1 allele and as CYP3A5-negative if they did not . Area under the plasma concentration-time curves (AUCs) from 0 to 6 hours (AUC(t)) and maximum postdose plasma concentration (C(max)) after a single dose and on day 5 of a twice-daily regimen were calculated and correlated with genotypes . RESULTS: ABT-773 AUC(t) and C(max) were, on average, higher in CYP3A5-negative subjects given 450 mg ABT-773 (n = 9) than in CYP3A5-positive subjects with identical doses (n = 8) . The relationship for AUC(t) was statistically significant both after a single dose (geometric mean and 95% confidence interval {CI}, 5.0 microg.h/mL {3.9-6.4 microg.h/mL} versus 2.8 microg.h/mL {1.8-4.3 microg.h/mL}; P =.03) and on the fifth day of twice-daily dosing (12.4 microg.h/mL {8.7-17.6 microg.h/mL} versus 7.4 microg.h/mL {5.5-9.8 microg.h/mL}, P =.04) . The relationship for C(max) was statistically significant after a single dose (1220 microg/mL {867-1167 microg/mL} versus 727 microg/mL {506-1044 microg/mL}, P =.04) and showed a trend in the same direction on the fifth day of twice-daily dosing (2566 microg/mL {1813-3631 microg/mL} versus 1621 microg/mL {1122-2343 microg/mL}, P =.07) . In contrast, AUC(t) and C(max) were not significantly different between CYP3A5-positive and CYP3A5-negative individuals given 150 mg or 300 mg ABT-773 . ABT-773 plasma levels did not trend with MDR-1 genotypes . CONCLUSIONS: These results suggest that CYP3A5 genotype may be an important determinant of in vivo drug disposition and that this effect may be dose-dependent. FEBS Lett, 2004 Jun 4, 567(2-3), 316 - 20 Insights into the specificity of RNA cleavage by the Escherichia coli MazF toxin; Munoz-Gomez AJ et al.; The mazEF (chpA) toxin-antitoxin system of Escherichia coli is involved in the cell response to nutritional and antibiotic stresses as well as in bacterial-programmed cell death . Valuable information on the MazF toxin was derived from the determination of the crystal structure of the MazE/MazF complex and from in vivo data, suggesting that MazF promoted ribosome-dependent cleavage of messenger RNA . However, it was concluded from recent in vitro analyses using a MazF-(His6) fusion protein that MazF was an endoribonuclease that cleaved messenger RNA specifically at 5'-ACA-3' sites situated in single-stranded regions . In contrast, our work reported here shows that native MazF protein cleaves RNA at the 5' side of residue A in 5'-NAC-3' sequences (where N is preferentially U or A) . MazF-dependent cleavage occurred at target sequences situated either in single- or double-stranded RNA regions . These activities were neutralized by a His6-MazE antitoxin . Although essentially consistent with previous in vivo reports on the substrate specificity of MazF, our results strongly suggest that the endoribonuclease activity of MazF may be modulated by additional factors to cleave messenger and other cellular RNAs. Soc Sci Med, 2004 Aug, 59(4), 763 - 73 A social disease/a social response: lessons in tuberculosis from early 20th century Chile; Paluzzi JE; During the 1930s, Chile reported the world's highest mortality rate due to tuberculosis . In this pre-antibiotic era, the attention of the biomedical community frequently turned to the underlying social inequalities and deficiencies that created conditions of heightened risk for Chile's rapidly expanding working class . With the recognition that crowded housing, chronic malnutrition and substandard working conditions fostered an environment in which the disease developed and spread with virulent rapidity, physicians frequently became vocal advocates for widespread and significant social reform . However, by the time of the introduction of efficacious pharmaceutical agents in the 1940s and with the overall rapid development of biomedicine in the mid-20th century, the larger medical discourse became more rigidly defined and characterized by the promotion of the new antibiotics and treatments . These factors increased the depth of the self-defined medical territory but substantially reduced its breadth . Accompanying this shift was an increasing focus on individual behaviors that were seen as deficient and were both socially censored and used as explanations for increased susceptibility . In the midst of the current worldwide epidemic of tuberculosis, this disease and its epidemiological pattern heightens our awareness of the significance and consequences of global inequalities . It also draws our attention to the importance of intervention within the social conditions from which these patterns emerge. Eur Respir J, 2004 May, 23(5), 714 - 7 Clarithromycin reduces the severity of bronchial hyperresponsiveness in patients with asthma; Kostadima E et al.; A randomised double-blind placebo-controlled study was designed to evaluate the effects of a semisynthetic macrolide